Toldo Stefano, Mezzaroma Eleonora, Bressi Edoardo, Marchetti Carlo, Carbone Salvatore, Sonnino Chiara, Van Tassell Benjamin W, Abbate Antonio
*Virginia Commonwealth University Pauley Heart Center, Virginia Commonwealth University, Richmond, VA; †Victoria Johnson Research Laboratories, Virginia Commonwealth University, Richmond, VA; and ‡Department of Pharmacotherapy and Outcome Studies, Virginia Commonwealth University, Richmond, VA.
J Cardiovasc Pharmacol. 2014 Jul;64(1):1-6. doi: 10.1097/FJC.0000000000000106.
Interleukin-1β (IL-1β) modulates the inflammatory response during acute myocardial infarction (AMI) and progression to ischemic cardiomyopathy. We investigated whether blockade of IL-1β after the onset of the cardiac dysfunction prevented left ventricular (LV) adverse remodeling in a mouse model of anterior nonreperfused AMI.
Infarct size and LV systolic function were assessed by echocardiography 7 days after coronary artery ligation. Mice with large infarct size and LV ejection fraction (LVEF) <40% were randomly assigned to treatment with a monoclonal antibody directed toward IL-1β antibody (10 mg/kg IL-1β-AB) or with a cyclosporine directed antibody (10 mg/kg control-AB). Echocardiogram was repeated after 10 weeks, followed by assessment of contractile reserve using isoproterenol challenge and LV catheterization.
After 10 weeks, control-AB-treated mice showed significantly increased LV end-diastolic diameter (+15%, P < 0.001) and decreased LVEF (-18%, P = 0.050). IL-1β-AB had no significant effect on LV end-diastolic diameter (+10%, P = 0.25 vs. control-AB) but significantly prevented LVEF reduction (+7%, P = 0.031 vs. control-AB), enlargement of the right ventricle (P = 0.024), impairment in myocardial performance index (P = 0.028) and contractile reserve (P = 0.008), and increased LV end-diastolic pressure (P = 0.030).
IL-1β blockade using a monoclonal antibody in mice with severe LV dysfunction after AMI prevents further deterioration in LV systolic and diastolic function and restores contractile reserve.
白细胞介素-1β（IL-1β）在急性心肌梗死（AMI）期间调节炎症反应，并在进展为缺血性心肌病过程中发挥作用。我们研究了在心脏功能障碍发生后阻断IL-1β是否能预防前壁非再灌注AMI小鼠模型中的左心室（LV）不良重塑。
冠状动脉结扎7天后，通过超声心动图评估梗死面积和左心室收缩功能。将梗死面积大且左心室射血分数（LVEF）<40%的小鼠随机分为两组，分别用针对IL-1β的单克隆抗体（10 mg/kg IL-1β-AB）或环孢素定向抗体（10 mg/kg对照-AB）进行治疗。10周后重复超声心动图检查，随后使用异丙肾上腺素激发试验和左心室导管插入术评估收缩储备。
10周后，对照-AB治疗的小鼠左心室舒张末期直径显著增加（+15%，P<0.001），LVEF降低（-18%，P = 0.050）。IL-1β-AB对左心室舒张末期直径无显著影响（+10%，与对照-AB相比P = 0.25），但显著预防了LVEF降低（+7%，与对照-AB相比P = 0.031）、右心室扩大（P = 0.024）、心肌性能指数受损（P = 0.028）和收缩储备受损（P = 0.008），并降低了左心室舒张末期压力（P = 0.030）。
在AMI后严重左心室功能障碍的小鼠中使用单克隆抗体阻断IL-1β可防止左心室收缩和舒张功能进一步恶化，并恢复收缩储备。
